進而影響卵泡生長與品質‧
http://humrep.oxfordjournals.org/content/22/3/676.full
Endocrine profile in serum and follicular fluid differs after ovarian stimulation with HP-hMG or recombinant FSH in IVF patients
- J. Smitz1,5,
- A.N. Andersen2,
- P. Devroey3,
- J.-C. Arce4 and
- for the MERIT Group*
+Author Affiliations
- 5To whom correspondence should be addressed at: Follicle Biology Laboratory and Center for Reproductive Medicine of the Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. E-mail: johan.smitz@az.vub.ac.be
- Received May 29, 2006.
- Revision received September 7, 2006.
- Revision received October 10, 2006.
- Accepted October 19, 2006.
Abstract
BACKGROUND: Highly purified menotrophin (HP-hMG) has been associated with fewer oocytes retrieved and a higher proportion of top-quality embryos compared with recombinant FSH (rFSH). METHODS: A randomized, assessor-blind, multinational trial in 731 women undergoing IVF after stimulation with HP-hMG (MENOPUR) (n = 363) or rFSH (GONAL-F) (n = 368) following a long GnRH agonist protocol was conducted. Blood was collected before, during and after stimulation. Fluid was collected from follicles ≥17 mm. RESULTS: Serum androstenedione, total testosterone and free androgen index (FAI) were higher (P< 0.001) with HP-hMG than with rFSH after starting stimulation. At the end of stimulation, serum estradiol was higher (P = 0.031) with HP-hMG, whereas progesterone was higher (P < 0.001) with rFSH, even after adjusting for ovarian response. Serum LH was not different between treatments. Mean mid- and end-follicular hCG levels in the HP-hMG group were 2.5 and 2.9 IU/l, respectively. Follicular fluid levels of FSH, LH, hCG, androstenedione, testosterone, FAI and estradiol and ratios of estradiol : androstenedione, estradiol : total testosterone and estradiol : progesterone were higher (P < 0.001) with HP-hMG, whereas progesterone was higher (P < 0.001) with rFSH. CONCLUSION: Major differences in serum and follicular fluid endocrine profile exist after stimulation with HP-hMG or rFSH. Exogenous LH activity induces a differential endocrine environment influencing oocyte quantity and quality, which may be of relevance for clinical outcome.
Table III.
Serum hormone concentrations on day 6, at the end of stimulation and at the time of oocyte retrieval after stimulation with highly purified menotrophin (HP-hMG) or recombinant FSH (rFSH)
| HP-hMG (n = 363) | rFSH (n = 368) | P-valuea | |
|---|---|---|---|
| Day 6 of stimulation | |||
| FSH (IU/l) | 15.8 ± 3.5 | 15.2 ± 3.5 | 0.009 |
| LH (IU/l) | 1.4 ± 0.8 | 1.4 ± 0.8 | 0.465 |
| hCG (IU/l) | 2.45 ± 0.80 | − | − |
| Estradiol (nmol/l) | 1.0 ± 0.9 | 1.1 ± 1.0 | 0.004 |
| Progesterone (nmol/l) | 1.4 ± 0.6 | 1.5 ± 0.7 | 0.333 |
| Androstenedione (nmol/l) | 6.0 ± 2.5 | 5.5 ± 2.4 | 0.002 |
| Total testosterone (nmol/l) | 0.89 ± 0.45 | 0.77 ± 0.41 | <0.001 |
| SHBG (nmol/l) | 55 ± 23 | 57 ± 22 | 0.188 |
| FAI | 1.96 ± 1.46 | 1.59 ± 1.09 | <0.001 |
| Last stimulation day | |||
| FSH (IU/l) | 18.3 ± 6.0 | 16.3 ± 4.7 | <0.001 |
| LH (IU/l) | 1.8 ± 0.9 | 1.7 ± 0.9 | 0.125 |
| hCG (IU/l) | 2.94 ± 1.18 | − | − |
| Estradiol (nmol/l) | 7.2 ± 4.3 | 6.6 ± 4.0 | 0.031 |
| Progesterone (nmol/l) | 2.6 ± 1.3 | 3.4 ± 1.7 | <0.001 |
| Androstenedione (nmol/l) | 11.9 ± 5.2 | 9.5 ± 3.8 | <0.001 |
| Total testosterone (nmol/l) | 1.71 ± 0.88 | 1.31 ± 0.65 | <0.001 |
| SHBG (nmol/l) | 88 ± 39 | 89 ± 38 | 0.729 |
| FAI | 2.23 ± 1.36 | 1.66 ± 0.96 | <0.001 |
| Oocyte retrieval | |||
| FSH (IU/l) | 9.6 ± 3.6 | 7.8 ± 2.8 | <0.001 |
| LH (IU/l) | 0.3 ± 0.0 | 0.3 ± 0.2 | 0.397 |
| hCG (IU/l) | 108.21 ± 31.11 | 104.11 ± 32.79 | 0.055 |
| Estradiol (nmol/l) | 3.9 ± 2.1 | 3.4 ± 1.9 | 0.001 |
| Progesterone (nmol/l) | 24.5 ± 15.6 | 36.3 ± 25.0 | <0.001 |
| Androstenedione (nmol/l) | 13.6 ± 5.5 | 10.8 ± 4.2 | <0.001 |
| Total testosterone (nmol/l) | 2.42 ± 1.13 | 1.77 ± 0.82 | <0.001 |
| SHBG (nmol/l) | 129 ± 54 | 129 ± 53 | 0.893 |
| FAI | 2.19 ± 1.40 | 1.61 ± 1.03 | <0.001 |
- SHBG, sex hormone-binding globulin.
- Data are mean ± standard deviations.
- The findings of the multi-adjusted analysis differ from the table above with respect to the following: day 6—progesterone was significantly lower with HP-hMG (P < 0.001); last stimulation day—estradiol was not significantly different (P = 0.550), SHBG was significantly lower with HP-hMG (P = 0.023); oocyte retrieval—LH was significantly lower with HP-hMG (P < 0.001), estradiol was not significantly different (P = 0.515).
Figure 1.
Serum profiles during stimulation (day 1, day 6, last simulation day and oocyte retrieval) with highly purified menotrophin (HP-hMG) and recombinant FSH (rFSH). The graphs illustrate the level of each hormone displayed by the ratio of the concentration in the HP-hMG group to the concentration in the rFSH group (ratio > 1: HP-hMG > rFSH). The point indicates the HP-hMG : rFSH ratio, and the vertical lines illustrate the 95% confidence interval. If the point is above 1, it means that the concentration is higher in the HP-hMG group than in the rFSH group. If the 95% confidence interval does not include 1, the difference between HP-hMG and rFSH is significant (P < 0.05). The analysis is adjusted for age strata. LSD, last stimulation day; OR, oocyte retrieval.
Table IV.
Serum hCG concentrations on day 6 in patients treated with highly purified menotrophin (HP-hMG) and clinical outcome (ongoing pregnancy rate, number of top-quality embryos and patients with top-quality embryos)
| Ongoing pregnancy rate | Number of top-quality embryos | Patients with top-quality embryos | |
|---|---|---|---|
| Serum hCG on day 6 | |||
| <25% (n = 87) | 15% | 0.6 | 33% |
| 25–50% (n = 88) | 25% | 0.8 | 48% |
| 50–75% (n = 90) | 33% | 1.2 | 49% |
| >75% (n = 90) | 33% | 1.3 | 57% |
| P-value, trend analysisa | 0.008 | 0.002 | 0.003 |
| P-value, trend analysisb | 0.081 | 0.004 | 0.009 |
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